Chemotherapy
Chemotherapy primarily refers to the treatment of cancer with one or more drugs that inhibit the growth of malignant cells as part of a regimen. Certain chemotherapy agents also have a role in the treatment of other conditions, including ankylosing spondylitis, multiple sclerosis, Crohn's disease, psoriasis, psoriatic arthritis, rheumatoid arthritis and scleroderma. The most common chemotherapy agents act by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that chemotherapy also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract, and hair follicles. This results in the most common side-effects of chemotherapy: decreased production of blood cells, hence also immunosuppression), inflammation of the lining of the digestive tract, and hair loss. Newer anticancer drugs act directly against abnormal proteins in cancer cells; this is termed “targeted therapy” and, in the technical sense, is not chemotherapy. History The first use of drugs to treat cancer was in the early 20th century, although it was not originally intended for that purpose. Mustard gas was used as a chemical warfare agent during World War I and was discovered to be a potent suppressor of blood production. A similar family of compounds known as nitrogen mustards were studied further during World War II at Yale University. It was reasoned that an agent that damaged the rapidly growing white blood cells might have a similar effect on cancer. Therefore, in December 1942, several patients with advanced lymphoma (cancers of certain white blood cells) were given the drug by vein, rather than by breathing the irritating gas. Concurrently, during a military operation in World War II, following a German air raid on the Italian harbour of Bari, several hundred people were accidentally exposed to mustard gas, which had been transported there by the allied forces to prepare for possible retaliation in the event of German use of chemical warfare. The survivors were later found to have very low white blood cell counts. After WWII was over and the reports declassified, the experiences converged and led researchers to look for other substances that might have similar effects against cancer. The first chemotherapy drug to be developed from this line of research was mustine. Since then, many other drugs have been developed to treat cancer, and drug development has exploded into a multibillion-dollar industry, although the principles and limitations of chemotherapy discovered by the early researchers still apply. The term chemotherapy The word "chemotherapy" without a modifier usually refers to cancer treatment, but its historical meaning is broader. The term was historically used for non-oncological references, such as the use of antibiotics (antibacterial chemotherapy). The first modern chemotherapeutic agent was arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis. This was later followed by sulfonamide (sulfa drugs) and penicillin. Other uses that have been termed chemotherapy are the treatment of autoimmune diseases such as multiple sclerosis, dermatomyositis, polymyositis, lupus, and rheumatoid arthritis. Principles Cancer is the uncontrolled growth of cells coupled with malignant behavior: invasion and metastasis. Cancer is thought to be caused by the interaction between genetic susceptibility and environmental toxins. In the broad sense, most “chemotherapeutic” drugs work by impairing cell division, effectively targeting fast-dividing cells. As these drugs cause damage to cells, they are termed “catatonic“. Some drugs cause cells to undergo so-called “self-programmed cell death“. Scientists have yet to identify specific features of malignant and immune cells that would make them uniquely targetable (barring some recent examples, such as the Philadelphia chromosome as targeted by imatinib). This means that other fast-dividing cells, such as those responsible for hair growth and for replacement of the intestinal lining, are also often affected. However, some drugs have a better side effect profile than others, enabling doctors to adjust treatment regimens to the advantage of patients in certain situations. As chemotherapy affects cell division, tumors with high growth fractions (such as acute myelogenous leukemia and the aggressive lymphomas, including Hodgkin's disease) are more sensitive to chemotherapy, as a larger proportion of the targeted cells are undergoing cell division at any time. Malignancies with slower growth rates, such as indolent lymphomas, tend to respond to chemotherapy much more modestly. Drugs affect "younger" tumors (i.e., more differentiated) more effectively, because mechanisms regulating cell growth are usually still preserved. With succeeding generations of tumor cells, differentiation is typically lost, growth becomes less regulated, and tumors become less responsive to most chemotherapeutic agents. Near the center of some solid tumors, cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumors is the fact that the chemotherapeutic agent often does not reach the core of the tumor. Solutions to this problem include radiation therapy (both brachytherapy and teletherapy) and surgery. Over time, cancer cells become more resistant to chemotherapy treatments. Recently, scientists have identified small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Research on p-glycoprotein and other such chemotherapy efflux pumps is currently ongoing. Medications to inhibit the function of p-glycoprotein are undergoing testing as of 2007 to enhance the efficacy of chemotherapy. Treatment schemes There are a number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms. “Combined modality chemotherapy” is the use of drugs with other cancer treatments, such as radiation therapy or surgery. Most cancers are now treated in this way. “Combination chemotherapy” is a similar practice that involves treating a patient with a number of different drugs simultaneously. The drugs differ in their mechanism and side effects. The biggest advantage is minimising the chances of resistance developing to any one agent. In “neoadjuvant chemotherapy” (preoperative treatment) initial chemotherapy is designed to shrink the primary tumor, thereby rendering local therapy (surgery or radiotherapy) less destructive or more effective. “Adjuvant chemotherapy” (postoperative treatment) can be used when there is little evidence of cancer present, but there is risk of recurrence. This can help reduce chances of relapse. It is also useful in killing any cancerous cells that have spread to other parts of the body. This is often effective as the newly growing tumours are fast-dividing, and therefore very susceptible. “Palliative chemotherapy” is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, a better toxicity profile is generally expected. All chemotherapy regimens require that the patient be capable of undergoing the treatment. Performance status is often used as a measure to determine whether a patient can receive chemotherapy, or whether dose reduction is required. Because only a fraction of the cells in a tumor die with each treatment (fractional kill), repeated doses must be administered to continue to reduce the size of the tumor. Types The majority of chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents. All of these drugs affect cell division or DNA synthesis and function in some way. Some newer agents do not directly interfere with DNA. These include monoclonal antibodies and the new tyrosine kinase inhibitors such as imatinib (Gleevec or Glivec), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors). These are examples of targeted therapies. In addition, some drugs that modulate tumor cell behaviour without directly attacking those cells may be used. Hormone treatments fall into this category. Alkylating agents Alkylating agents are so named because of their ability to interfere with many of the chemical reactions that take place under conditions present in cells. Cisplatin and carboplatin, as well as oxaliplatin, are alkylating agents. They impair cell function by forming covalent bonds with the amino, carboxyl, sulfhydryl, and phosphate groups in biologically important molecules. Other agents are mechlorethamine, cyclophosphamide, chlorambucil, and ifosfamide. They work by chemically modifying a cell's DNA. Anti-metabolites Anti-metabolites masquerade as purines (azathioprine, mercaptopurine or pyrimidines)—which become the building-blocks of DNA. They prevent these substances from becoming incorporated in to DNA during the "S" phase of the cell cycle, stopping normal development and division. They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used to prevent cell growth. Plant alkaloids and terpenoids These alkaloids are derived from plants and block cell division by preventing microtubules that are vital to the formation of structures in the cell from functioning. Microtubules are vital for cell division, and, without them, cell division cannot occur. The main examples are vinca alkaloids and taxanes. Vinca alkaloids Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules (the “M phase” of the cell cycle). They are derived from the Madagascar periwinkle, (Catharanthus roseus) The vinca alkaloids include Vincristine, Vinblastine, Vinorelbine and Vindesine Podophyllotoxin Podophyllotoxin is a plant-derived compound that is said to help with digestion as well as used to produce two other cytostatic drugs, etoposide and teniposide. They prevent the cell from entering the “G1 phase” (the start of DNA replication) and the replication of DNA (the “S phase“). The exact mechanism of its action is not yet known. The substance has been primarily obtained from the American Mayapple (Podophyllum peltatum). Recently it has been discovered that a rare Himalayan Mayapple (Podophyllum hexandrum) contains it in a much greater quantity, but, as the plant is endangered, its supply is limited. Studies have been conducted to isolate the genes involved in the substance's production, so that it could be obtained with the use of recombinant DNA technology (i.e. “gene splicing”) Taxanes The prototype taxane is the natural product paclitaxel, originally known as Taxol and first derived from the bark of the Pacific Yew. Docetaxel is a semi-synthetic analogue of paclitaxel. Taxanes enhance stability of microtubules, preventing the separation of chromosomes to opposite sides of a cell just after the chromosomes duplicate. Topoisomerase inhibitors Topoisomerases are essential enzymes that maintain the shape and structure of DNA. Inhibition of type I or type II topoisomerases interferes with both transcription and replication of DNA by preventing DNA from coiling properly. Some type I topoisomerase inhibitors include the camptothecins: irinotecan and topotecan. Examples of type II inhibitors include amsacrine, etoposide and teniposide. These are semisynthetic derivatives of epipodophyllotoxins, alkaloids naturally occurring in the root of American Mayapple. Cytotoxic antibiotics These include dactinomycin, anthracyclines, (doxorubicin, daunorubicin, valrubicin, idarubicin, epirubicin, which also inhibit topoisomerase II), other cytotoxic antibiotics, bleomycin, plicamycin, and mitomycin Newer and experimental approaches Isolated infusion approaches Isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used to treat some tumours. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumor sites without causing overwhelming systemic damage. These approaches can help control solitary or limited metastases, but they are by definition not systemic, and, therefore, do not treat distributed metastases or micrometastases. Targeted delivery mechanisms Specially targeted delivery vehicles aim to increase effective levels of chemotherapy for tumor cells while reducing effective levels for other cells. This should result in an increased tumor kill and/or reduced toxicity. Specially targeted delivery vehicles have a differentially higher affinity for tumor cells by interacting with tumor-specific or tumor-associated antigens. In addition to their targeting component, they also carry a payload - whether this is a traditional chemotherapeutic agent, or a radioisotope, or an immune-stimulating factor. Specially targeted delivery vehicles vary in their stability, selectivity, and choice of target, but, in essence, they all aim to increase the maximum effective dose that can be delivered to the tumor cells. Reduced systemic toxicity means that they can also be used in sicker patients, and that they can carry new chemotherapeutic agents that would have been far too toxic to deliver via traditional systemic approaches. Nanoparticles Nanoparticles have emerged as a useful vehicle for poorly soluble agents such as paclitaxel. Protein-bound paclitaxel (e.g., Abraxane) or nab-paclitaxel was approved by the FDA in January 2005 for the treatment of refractory breast cancer. This formulation of paclitaxel uses human albumin as a vehicle and not the Cremophor vehicle used in Taxol. Nanoparticles made of magnetic material can also be used to concentrate agents at tumour sites using an externally applied magnetic field. Electrochemotherapy Electrochemotherapy is the combined treatment in which injection of a chemotherapeutic drug is followed by application of high-voltage electric pulses locally to the tumor. The treatment enables the chemotherapeutic drugs, which otherwise cannot or hardly go through the membrane of cells (such as bleomycin and cisplatin), to enter the cancer cells. Hence, greater effectiveness of antitumor treatment is achieved. Clinical electrochemotherapy has been successfully used for treatment of cutaneous and subcutaneous tumors irrespective of which tissue gave rise to the cancerous cells. The method has been reported as safe, simple and highly effective in all reports on clinical use of electrochemotherapy. According to the ESOPE project (European Standard Operating Procedures of Electrochemotherapy), the Standard Operating Procedures for electrochemotherapy were prepared, based on the experience of the leading European cancer centres on electro chemotherapy. Recently, new electrochemotherapy modalities have been developed for treatment of internal tumors using surgical procedures, endoscopic routes or percutaneous approaches to gain access to the treatment area. Dosage Dosage of chemotherapy can be difficult: If the dose is too low, it will be ineffective against the tumor, whereas, at excessive doses, the toxicity (side-effects, neutropenia) will be intolerable to the patient. This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity. In immunotherapy, they are in principle used in smaller dosages than in the treatment of malignant diseases. In most cases, the dose is adjusted for the patient's body surface area, a measure that correlates with blood volume. In Whatever It Takes, Wilson actually quotes a dose in milligrams per square metre of body area for the chemotherapy to be used on John at the CIA. The BSA is usually calculated with a mathematical formula or a nomogram, using a patient's weight and height, rather than by direct measurement. Delivery Most chemotherapy is delivered intravenously, although a number of agents can be administered orally (e.g., melphalan, busulfan, capecitabine). In some cases, isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumour sites without causing overwhelming systemic damage. Depending on the patient, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, intravenous chemotherapy may be given on either an inpatient or an outpatient basis. For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly used systems are the Hickman line, the Port-a-Cath, and the PICC line. These have a lower infection risk, are much less prone to phlebitis or extravasation, and abolish the need for repeated insertion of peripheral tubes. Harmful and lethal toxicity from chemotherapy limits the dosage of chemotherapy that can be given. Some tumors can be destroyed by sufficiently high doses of chemotherapeutic agents. However, these high doses cannot be given because they would be fatal to the patient. Adverse effects Chemotherapeutic techniques have a range of side-effects that depend on the type of medications used. The most common medications affect mainly the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines. Common side-effects include: *Depression of the immune system (immunosuppression), which can result in potentially fatal infections. Although patients are encouraged to wash their hands, avoid sick people, and take other infection-reducing steps, about 85% of infections are due to naturally occurring microorganisms in the patient's own gastrointestinal tract (including the oral cavity) and skin. This may manifest as systemic infections, such as sepsis, or as localized outbreaks, such as herpes, shingles, or other members of the human herpes virus family. Sometimes, chemotherapy treatments are postponed because the immune system is suppressed to a critically low level. *Fatigue. The treatment can be physically exhausting for the patient, who might already be very tired from cancer-related fatigue. It may produce mild to severe anemia. Treatments to mitigate anemia include hormones to boost blood production (erythropoietin), iron supplements, and blood transfusions. *Tendency to bleed easily. Medications that kill rapidly dividing cells or blood cells are likely to reduce the number of platelets in the blood, which can result in bruises and bleeding. Extremely low platelet counts may be temporarily boosted through platelet transfusions. Sometimes, chemotherapy treatments are postponed to allow platelet counts to recover. * Gastrointestinal distress. Nausea and vomiting are common side-effects of chemotherapeutic medications that kill fast-dividing cells. This can also produce diarrhea or constipation. Malnutrition and dehydration can result when the patient does not eat or drink enough, or when the patient vomits frequently, because of gastrointestinal damage. This can result in rapid weight loss, or occasionally in weight gain, if the patient eats too much in an effort to allay nausea or heartburn. Weight gain can also be caused by some steroid medications. These side-effects can frequently be reduced or eliminated with antiemetic drugs. Self-care measures, such as eating frequent small meals and drinking clear liquids or ginger tea, are often recommended. This is a temporary effect, and frequently resolves within a week of finishing treatment. *Hair loss. Some medications that kill rapidly dividing cells cause dramatic hair loss; other medications may cause hair to thin. These are most often temporary effects: hair usually starts to regrow a few weeks after the last treatment, sometimes with a tendency to curl, resulting in "chemo curls." Permanent hair loss can result from some standard chemotherapy regimens. Scalp cooling offers a means of preventing both permanent and temporary hair loss. Damage to specific organs is possible: *Cardiotoxicity (heart damage) *Hepatotoxicity (liver damage) *Nephrotoxicity (kidney damage) *Ototoxicity (damage to the inner ear), producing vertigo *Encephalopathy (brain dysfunction) Immunosuppression and myelosuppression Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells, and platelets. Anemia and thrombocytopenia, when they occur, are improved with blood transfusion. Neutropenia (a decrease of the neutrophil granulocyte count) can be improved with synthetic G-CSF e.g., filgrastim or lenograstim. In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells that produce white and red blood cells) are destroyed, meaning bone marrow transplants are necessary. However, some patients still develop diseases because of this interference with bone marrow. In Japan, the government has approved the use of some medicinal mushrooms like Trametes versicolor, to counteract depression of the immune system in patients undergoing chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) Nausea and vomiting are two of the most feared cancer treatment-related side-effects for cancer patients and their families. In 1983, Coates and his colleagues. found that patients receiving chemotherapy ranked nausea and vomiting as the first and second-most-severe side-effects, respectively. Up to 20% of patients receiving agents that posed a high risk of vomiting in this era postponed, or even refused, potentially curable treatments. Chemotherapy-induced nausea and vomiting (CINV) are common with many treatments and some forms of cancer. Since the 1990s, several novel classes of antiemetics have been developed and commercialized, becoming a nearly universal standard in chemotherapy regimens, and helping to successfully manage these symptoms in a large portion of patients. Effective mediation of these unpleasant and sometimes-crippling symptoms results in increased quality of life for the patient and more efficient treatment cycles, due to less stoppage of treatment due to better tolerance by the patient, and due to better overall health of the patient. Secondary cancers Development of secondary neoplasia after successful chemotherapy and/or radiotherapy treatment can occur. The most common secondary neoplasm is secondary acute myeloid leukemia, which develops primarily after treatment with alkylating agents or topoisomerase inhibitors. Survivors of childhood cancer are more than 13 times as likely to get a secondary neoplasm during the 30 years after treatment than the general population. However, not all of this increase can be attributed to chemotherapy. Infertility Some types of chemotherapy can affect the reproductive organs and may cause infertility. Chemotherapies with high risk include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil, and chloromethane. Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin. On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin, and antimetabolites such as methotrexate, mercaptopurine, and 5-fluoruracil. Patients may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of semen, ovarian tissue, oocytes, or embryos. As more than half of cancer patients are elderly, this adverse effect is only relevant for a minority of patients. Teratogenicity Chemotherapy can potentially harm the fetus during pregnancy, especially during the first trimester, to the extent that abortion usually is recommended if pregnancy in this period is found during chemotherapy. Second- and third-trimester exposure does not usually increase the teratogenic risk and adverse effects on cognitive development, but it may increase the risk of various complications of pregnancy and suppression of the fetal immune system. In males previously having undergone chemotherapy or radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk. In females previously having undergone chemotherapy, miscarriage and congenital malformations are not increased in subsequent conceptions. However, when in-vitro fertilization and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence it has been recommended that the babies be screened. Neurological adverse effects Reported are cytotoxic-induced neuropathy causing pain or paralysis. Some patients report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment, referred to as “chemo brain” by patients' groups. Other side effects In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Although prophylaxis is available and is often initiated in patients with large tumors, this is a dangerous side-effect that can lead to death if left untreated. Less common side-effects include red skin, dry skin, damaged fingernails, a dry mouth xerostomia, water retention, and sexual impotence. Some medications can trigger allergic or pseudoallergic reactions. Specific chemotherapeutic agents are associated with organ-specific toxicities, including cardiovascular disease (e.g., doxorubicin), interstitial lung disease (e.g., bleomycin) and occasionally secondary neoplasm (e.g., MOPP therapy for Hodgkin's disease). Occupational precautions Healthcare workers exposed to antineoplastic agents take precautions to keep their exposure to a minimum. There is a limitation in cytotoxics dissolution in Australia and the United States to 20 dissolutions per pharmacist/nurse, since pharmacists that prepare these drugs or nurses that may prepare or administer them are the two occupational groups with the highest potential exposure to antineoplastic agents. In addition, physicians and operating room personnel may also be exposed through the treatment of patients. Hospital staff, such as shipping and receiving personnel, custodial workers, laundry workers, and waste handlers, all have potential exposure to these drugs during the course of their work. The increased use of antineoplastic agents in veterinary oncology also puts these workers at risk for exposure to these drugs. External links * Search for chemotherapy trials * American Cancer Society - Chemotherapy On the series The Sacrifice The episode Babies & Bathwater explored the ramifications on the choice a pregnant patient must make when chemotherapy may be harmful to the developing fetus. The patient, Naomi Randolph, had developed small cell lung cancer, a particularly fast growing and aggressive form of cancer with a very low survival rate. She needed experimental chemotherapy immediately. However, it was clear that the treatment would be fatal to Naomi's baby. The doctors recommended a Cesearean section because at 28 weeks, the fetus had an 80% chance of surviving the procedure. However, Naomi insisted on waiting two more weeks, at which point the baby would have a 90% chance of survival. Unbeknownst to the doctors, but later deduced by House, Naomi had lost a child in the past - a fact that was not known to her husband. She feared that her husband would, like she had been in the past, be overwhelmed by a sick child. Dr. House assured her that the hospital had the best neo-natal unit in the state and she finally agreed to the Cesearean. However, due to the intervention of Edward Vogler, who found out Naomi was not going to wait the required thirty days after a surgery to start chemotherapy, he cancelled the surgery and kept Naomi out of the clinical trial. Before the team could make alternative arrangements, Naomi developed complications and died. Luckily, her baby was saved when House convinced the husband to allow them to let Naomi die to save the baby. But it's not cancer In the appropriately named Not Cancer, Apple is the last of five patients who haven't died mysteriously after receiving a transplant from the same donor. The team starts to think it's cancer despit the fact it doesn't explain any of the other deaths, but although House is sure it isn't, he agrees to chemotherapy when they run out of time, ideas and treatment. Astoundingly, Apple starts to improve, but House is not convinced. He's sure the improvement is temporary and the chemotherapy is treating something that acts like cancer, but isn't. He can't convince Cuddy, and she's so worried that House will try his idea of brain surgery to find out what's wrong that she prohibits him from going near the patient. However, House convinces Lucas Douglas to switch out Apple's chemotheraphy for saline. She soon crashes and the doctors rush her into the operating room for brain surgery. Once she's opened up, House admits his deception, but with the risky part having been done, they proceed to test her brain and find House was right - cancerous stem cells have replaced genuine brain cells - she would have died if she had remained on chemo. They manage to destroy the cells and Apple soon recovers. The Serendipidous Misdiagnosis In Dying Changes Everything, House was distracted due to Wilson's decision to leave the hospital. After a series of misdiagnoses, Thirteen ruled out three other diagnoses of their paient Lou and favored a fourth, lymphoma. Foreman was unconvinced because the patient had no palpable lymph nodes. However, Foreman consulted with Wilson, who assured Foreman that lymphoma can appear without palpable lymph nodes. He ordered chemotherapy. Luckily, Lou started to feel better. Thirteen felt she had it right, but House came along and saw that the patient had substantially aged since the last time he saw her, more like her true age of 37. He quickly realized that lepramatous leprosy, a positive side effect of which is youthful looking skin, would also be killed by the chemotherapy, which is why she felt better. Lou was quickly switched to the correct treatment and fully recovered . The Job Saver At the beginning of Season 6, Cuddy allows Foreman one shot at House's old job when House announces he doesn't want to return. In Epic Fail, he treats Vince Pearson, a rich video game developer who has no patience for Foreman and instead posts his case on the internet. However, when the 'net gets it wrong, Foreman comes up with the diagnosis of Light-Chain Deposition Disorder, which mimics the amyloidosis the patient thought he had but is far more dangerous to treat and impossible to diagnose with tests. It needs high dose chemotherapy. Foreman convinces a terrified Vince to agree to treatment when Foreman says his job is on the line and Vince realizes his life is on the line. However, Foreman gets a break when the next morning, he has realizes the patient actually has Fabry disease. Luckily, Thirteen had already started him on the right treatment the previous night when she found that one of the internet commenters (who turned out to be House) suggested it as well and she realized it fit. The Celebration In the episode Wilson, Wilson and his friend (and former patient) Tucker celebrate Tucker's fifth year of remission by going hunting and taking the opportunity to shoot at a chemotheraphy bag. However, after the celebration, Tucker collapses and can't move his arm or leg. Back at the hospital, Wilson desperately tries to find a diagnosis that isn't cancer, even thought House is convinced it is. House turns out to be right - it's a form of leukemia that was caused by Tucker's original chemotherapy. Tucker needs more chemotheraphy, this time injected directly into the brain because in a bit of luck, the cancer is restricted there. Tucker's chances are good, but the first course of chemotherapy has no effect. Desperate for a cure, Wilson convinces Tucker to double the dose. It destroys the cancer within two days, but unfortunately destroy's Tucker's liver in the process. Withough a source of a transplant except Wilson, Tucker guilts Wilson into it. In a bit of irony, the incident weakens Wilson's friendship with Tucker, but strengthen's Wilson's bond to House. The Hail Mary In The C Word, when Wilson develops a stage II thymoma, he runs through six oncologists who all tell him the same thing - his chances are best if he goes with the standard course of radiation therapy followed by surgery. However, Wilson is terrified that the conservative course won't work and he will hang on in pain and ill for years trying to use increasingly aggressive therapy only when it's probably too late. He wants to try a short regimen of high dose chemotherapy, which will either reduce the size of the cancer to operable size, or show him that the cancer is untreatable. When House finds out, he reluctantly agrees to help Wilson by performing the treatment at 221B Baker Street. Wilson gets very sick, and at one point is in such bad shape that House insists on taking him to hospital. However, Wilson refuses,s aying he would rather die in House's apartment than at a hospital. House reluctantly agrees and, miraculously, survives the chemotherapy. Hoewever, a week later, they find it was all for naught when the scans show the thymoma wasn't affected by the treatment - it's inoperable and terminal. Other Uses *Lucy Palmeiro was given chemotherapy after her surgery to remove her liver tumor in The Socratic Method. *The Volleyball Player was successfully treated with chemotheraphy after surgery to remove a cancerous adenoma in her leg. *In Merry Little Christmas, Abigail Ralphean needed chemotherapy and surgery to treat her Langerhans cell histiocytosis *In It's a Wonderful Lie, Maggie's breast cancer was treated with chemotherapy. *In Joy to the World, one of the earlier diagnoses for Natalie Soellner was leukemia, and Wilson suggested chemotherapy to treat. *In Saviors, one of the differentials for Doug Svensen was cancer, and House ordered chemotherapy. *Chemotherapy had to be ruled out for Frankie in Private Lives, because even though they mistakenly thought she had lymphoma, it had spread throughout her body. *In 5 to 9, House treats Mr. Plutus with chemotherapy for his renal cell carcinoma. *In Teamwork, House ordered chemotheraphy for Hank Hardwick when they thought he had lymphoma. *In Baggage, House orders chemotherapy for Sidney Merrick when he feels that she has a prion disease that has spread to her brain stem. Other relevant articles on this Wiki *Methyltrexate *Cyclophosphamide *Mechlorethamine This article was largely developed from the article on the subject on Wikipedia http://en.wikipedia.org/wiki/Chemotherapy This article was the featured article for June, 2012. It was the first featured article to feature a treatment. Category:Pharmaceuticals Category:Oncology Category:Featured articles